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Research Article

Liposome-coated CaO2 nanoblockers for enhanced checkpoint blockade therapy by inhibiting PD-L1 de novo biosynthesis

Ruijun Che1,§, Dandan Han1,§, Fei Wang2,3, Huifang Liu4, Miao Fan1, Hongyu Yan1, Tingshan Xiao4, Zhaoshuo Wang1, Xiaohan Zhou2,3, Xueyi Wang2,3, Kaihan Zhang5, Caiwen Ou2,3, Jinchao Zhang1(), Zhenhua Li2,3()
College of Chemistry & Environmental Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, China
Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523059, China
Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Guangzhou 510515, China
College of Pharmaceutical Science, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, China
Department of Chemistry, the University of Manchester, Manchester M13 9PL, UK

§ Ruijun Che and Dandan Han contributed equally to this work.

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Graphical Abstract

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Herein, we proposed a beyond anti-programmed death ligand-1 (PD-L1)-based immune checkpoint blockade therapy by using liposomes-coated CaO2 (CaO2@Lipo) nanoparticles to inhibit the de novo biosynthesis of PD-L1.

Abstract

The blocking of the immune checkpoint pathway with antibodies, especially targeting to programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway, was currently a widely used treatment strategy in clinical practice. However, the shortcomings of PD-L1 antibodies were constantly exposed with the deepening of its research and their therapeutic effect was limited by the translocation and redistribution of intracellular PD-L1. Herein, we proposed to improve immune checkpoint blockade therapy by using liposomes-coated CaO2 (CaO2@Lipo) nanoparticles to inhibit the de novo biosynthesis of PD-L1. CaO2@Lipo would produce oxygen and reduce hypoxia-inducible factor-1α (HIF-1α) level, which then downregulated the expression of PD-L1. Our in vitro and in vivo results have confirmed CaO2@Lipo promoted the degradation of HIF-1α and then downregulated the expression of PD-L1 in cancer cells for avoiding immune escape. Furthermore, to mimicking the clinical protocol of anti-PD-L1 antibodies + chemo-drugs, CaO2@Lipo was combined with doxorubicin (DOX) to investigate the tumor inhibition efficiency. We found CaO2@Lipo enhanced DOX-induced immunogenic cell death (ICD) effect, which then promoted the infiltration of T cells, strengthened the blocking effect, and thus provided an effective means to overcome the traditional immune checkpoint blockade treatment.

Keywords

immune checkpoint blockade therapyoxygen-producinghypoxia-inducible factor-1α (HIF-1α)programmed death ligand-1 (PD-L1) redistributionimmunogenic cell death

Electronic Supplementary Material

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Nano Research
Volume 16 Issue 5,
May 2023
Pages 7227-7236
DOI: 10.1007/s12274-022-5362-7
Cite this article:
Che R, Han D, Wang F, et al. Liposome-coated CaO2 nanoblockers for enhanced checkpoint blockade therapy by inhibiting PD-L1 de novo biosynthesis. Nano Research, 2023, 16(5): 7227-7236. https://doi.org/10.1007/s12274-022-5362-7
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